Method for synthesis of acrylamide derivatives

Abstract

The present invention relates to a method for synthesis of an acrylamide derivative, starting with dissolving a salt of a nucleophilic amine in water to form an aqueous solution and desalting said solution with a base, comprising the following steps: a) addition of dissolved activated acrylic acid derivative to said solution; b) acidification of aqueous phase; and c) extraction of said aqueous phase.

1. A method for synthesis of an acrylamide derivative, starting with dissolving a salt of a nucleophilic amine in water to form an aqueous solution and desalting said solution with a base, comprising the following steps:
 a) addition of dissolved activated acrylic acid derivative to said solution; 
 b) acidification of aqueous phase; and 
 c) extraction of said aqueous phase. 
 
     
     
       2. The method of  claim 1 , wherein the acrylamide derivative is an immobiline. 
     
     
       3. The method of  claim 2 , wherein the acrylamide derivative is acrylamido agmatine. 
     
     
       4. The method of  claim 3 , wherein the salt is an agmatine salt. 
     
     
       5. The method of  claim 1 , wherein the extraction in step c) is performed with an organic solvent. 
     
     
       6. The method of  claim 5 , wherein the organic solvent is MIBK (methyl isobutyl ketone). 
     
     
       7. The method of  claim 1 , wherein the acrylic acid derivative is an activated acrylic acid derivative selected from the group consisting of acryloyl chloride, acrylic acid N-hydroxysuccinimide ester, pentafluorophenyl acrylate, pentachlorophenylacrylate, and 4-nitrophenyl acrylate. 
     
     
       8. The method of  claim 1 , wherein the desalting is with NaOH, TEA (triethylamine), DIPEA (diisopropylethylamine), or K 2 CO 3 . 
     
     
       9. The method of  claim 1 , further comprising fixing pH to 7. 
     
     
       10. The method of  claim 1 , comprising, before step b),
 i) basification of aqueous phase to a pH above the pKa of the organic base, and 
 ii) extraction of aqueous phase with an organic solvent to remove the organic base. 
 
     
     
       11. The method of  claim 1 , wherein agmatine sulphate is dissolved, desalted with K 2 CO 3  and comprising the following steps:
 a) addition of acryloyl chloride; 
 b) acidification to pH 1-4; 
 c) filtration; 
 d) extraction with MIBK; and 
 e) pH adjustment to pH 7. 
 
     
     
       12. The method of  claim 11 , wherein the acidification pH is 2.3.